NEUROPROTECTIVE PROPERTIES OF PLANT EXTRACT FROM LIMONIUM GMELINII

logic conditions. When excess ROS are present within the cell, this oxidative stress may have profound deleterious effects on the cell, including the direct oxidation of biomolecules (e.g., lipid, protein, and DNA), indirect alteration in cellular structures and functions, and the induction of cell death. The brain is one of the organs especially vulnerable to the effects of ROS because of its high oxygen demand and abundance of peroxidation-susceptible lipid cells. However, there are numerous data indicating that plant polyphenols are able to reduce oxidative stress and inflammatory processes associated with brain damage. As it was shown in previous studies, the extract of polyphenols isolated from the roots of Limonium gmelinii (a plant widespread on the territory of Kazakhstan) has a number of therapeutic properties. Here we investigated antioxidant and anti-inflammatory properties of polyphenols extract from L.gmelinii in astrocytes and cerebral endothelial cells (CECs) in vitro. Methods: Human primary astrocytes and mouse bEnd3 line of CECs were pre-treated with polyphenol extract of L.gmelinii followed by incubation in tumor necrosis factor alpha (TNF-α) or H2O2. The level of ROS generation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, P-selectin expression, and activity of extracellular signal–regulated kinases 1/2(ERK1/2) were evaluated by quantitative immunofluorescence analysis, confocal microscopy and mitogen-activated protein kinase (MAPK) assay. Results: It was shown that the extract of the L.gmelinii at a dosage of 30 μg/ml does not have a cytotoxic effect. Moreover, it neutralizes the toxic effect of TNF-α by blocking the formation of ROS in astrocytes, interfering with the activation of NADPH oxidase in astrocytes, mobilization of P-selectin on the surface of bEnd3 cells, and inhibiting the activity of protein kinase ERK1/2. Conclusion: It can be concluded that polyphenols extract from L.gmelinii has an antioxidant properties, neutralizes TNF-α-induced inflammatory processes in the brain cells and could be utilized for further in vivo examination

NEW TREATMENT STRATEGY AGAINST ISCHEMIC BRAIN DAMAGE BASED ON COMBINED APPLICATION OF STEM CELL THERAPY AND PLANT POLYPHENOLS

Introduction: There is a number of data indicating that plant polyphenols can provide protection against neurodegenerative changes associated with cerebral ischemia. On the other hand, it has been shown that application of bone marrow-derived mesenchymal stem cells (BM-MSCs) resulted in an improved functional recovery in animal models of cerebral ischemia and stroke by modulating the inflammatory response, and stimulating endogenous neurogenesis and angiogenesis. Thus, we hypothesized that neuroregenerative potential of mesenchymal stem cell therapy could be significantly improved if applied in combination with plant polyphenols. We applied extract of Limonium Gmelinii (a plant widespread in Kazakhstan) as a source of plant polyphenols. Methods: 25 female Wistar rats were used in this study (weight 280-300g). Ischemic stroke was induced in 20 animals by occlusion of the middle cerebral artery (MCAO); 15 animals received either Limonium Gmelini, or BM-MSCs, and both; untreated and intact animals served as controls. The day before the induction of stroke, the next day, on the 14th and 28th days after MCAO the sensorimotor functions of the animals were evaluated. Before transplantation, BM-MSCs were transfected with lentiviral particles. Results: The distribution of the transfected MSCs inside the body of laboratory animal with MCAO was shown to be different from the distribution of MSCs inside the body of intact rats (control group). In control rats all the MSCs were localized in visceral organs, while in rats with surgically induced MCAO some amount of cells was found in the brains. Daily treatment of rat with 200 mg/kg of Limonium Gmelinii extract for 28 days or single transplantation of MSC (5x10e6 cells) showed partial restoration of the locomotor function of the animals while combined therapy with Limonium Gmelinii and MSCs completely restores it by 28th day. Conclusion: Combined therapy with extract of Limonium Gmelinii and mesenchymal stem cells is a more effective approach in comparison to monotherapy

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension (‘PPCM-noHTN’); 2) women with hypertension but without pre-eclampsia (‘PPCM-HTN’); 3) women with pre-eclampsia (‘PPCM-PE’). Maternal (6-month) and neonatal outcomes were compared. Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p<0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p<0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87). Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM